Although ocular infections with herpes simplex virus type 1 (HSV-1) are a major cause of human corneal disease and blindness, as yet the mechanisms responsible for the pathological processes seen in association with HSV-1 induced ocular disease are not well-understood. It is thought that the pathology of HSV-1 eye disease is a result of viral factors, immunological factors or a combination of both. Other investigators have shown that an interesting pattern of bilateral disease results after the injection of HSV-1 into the anterior chamber of one eye. In the injected eye, there is an acute destructive inflammatory reaction in the anterior segment (cornea, anterior chamber) and the anterior portion of the uveal tract (iris and ciliary body) which occurs within three days of virus inoculation. The contralateral (uninoculated) eye exhibits a delayed destructive reaction which is limited to the posterior segment (vitreous, retina, choroid) and the iris of that eye only. The cornea of the uninjected eye is spared while the retina of this eye is destroyed; the cornea and retina of the injected eye show the reverse pattern of destruction. Using a mouse (BALB/c) model, the aim of the research proposed herein is (a) to discover when and by what route HSV-1 spreads from the inoculated eye to the uninoculated eye following placement of the virus into the anterior chamber of one eye and (b) to explore further the mechanism by which the retina of the contralateral eye is destroyed following HSV-1 inoculation by determining if viral defective interfering (DI) particles play a role in destruction of the retina of the contralateral eye and sparing of the retina of the injected eye. Since HSV-1 is an excellent producer of DI particles in situations where the virus is being replicated to high titer, production of these particles may serve to protect the retina of the injected eye by inhibiting viral replication. The goals of this project will be achieved using molecular hybridization and immunoperoxidase viral antigen staining techniques to extend the findings from gross and microscopic examinations of HSV-1 inoculated and uninoculated eyes. Results from these studies will identify the route of viral progression in HSV-1-induced ocular disease and allow a better definition of the role of HSV-1 DI particles in and their relationship to ocular viral pathogenesis.